This is the continuation of a long-range study of the effects of purine antimetabolites on tumor cells and various normal tissues. The action of the tight-binding inhibitor of adenosine deaminase, deoxycoformycin, on the metabolism of adenosine and its analogs is under study where marked enhancement of the incorporation of certain adenosine analogs into nucleotide pools is observed. The effect on intracellular PRPP levels of alterations in normal and analog nucleotide levels is under investigation with murine Sarcoma 180 cells. The rate of inactivation and reactivation of intracellular adenosine deaminase by inhibitors such as deoxycoformycin is under study. A variety of adenosine analogs is examined for effects on the nucleotide pools and ADP-induced aggregation of human blood platelets. Various new adenosine analogs prepared by the group of Professor Leroy Townsend are being tested for biological activity by measuring such phenomena as incorporation into nucleotide pools, inhibition of blood platelets and reactivity with various enzymes of purine metabolism. Inhibitors of adenosine deaminase, such as coformycin and deoxycoformycin, are examined for action on various aspects of purine metabolism, including the enzyme 5'-AMP deaminase where marked inhibition by coformycin has been observed. The action of the inhibitors of adenosine analogs on the adenylate cycle is under study.